NDA Submitted for Duvelisib for CLL and Follicular Lymphoma

Wednesday, May 30, 2018

A New Drug Application (NDA) was submitted for the oral phosphoinositide 3-kinase (PI3K) dual inhibitor duvelisib for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) and relapsed/refractory follicular lymphoma (FL). The NDA was supported by data from the phase III DUO trial and the phase II DYNAMO study.

In the DUO trial, 319 patients with relapsed/refractory CLL/SLL were randomized 1:1 to receive duvelisib 25 mg twice-daily or ofatumumab 300 mg on day one, followed by seven weekly infusions and four monthly infusions of 2,000 mg. Duvelisib reduced the risk of disease progression or death by 48 percent, compared with ofatumumab, and more patients responded to duvelisib than ofatumumab (73.8% vs. 45.3%; p<0.0001 for both). The median progression-free survival (PFS) was longer among those treated with duvelisib (13.3 vs. 9.9 months; hazard ratio [HR] = 0.52; p<0.0001), including in patients with the del17p mutation (12.7 vs. 9.0 months; HR=4.1; p=0.0011). Overall survival (OS) was similar between the two treatment cohorts (p=0.48).

The open-label DYNAMO study included 129 patients with indolent non- Hodgkin lymphoma, including 83 with FL, who were refractory to rituximab and chemotherapy or radio-immunotherapy. Patients received continuous duvelisib 25 mg twice-daily. Duvelisib led to an objective response rate of 46 percent in the entire population and 41 percent in the subgroup of patients with FL (p<0.0001). The median OS in the entire population was 18.4 months, while the PFS was 8.4 months (ranges not reported).